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Communications Chemistry· 2026Q1

ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer

Hezheng Lyu, Hassan Gharibi, Bohdana Sokolova, Mücahit Varlı et al.

Short summary

A new database, ThermoTargetMiner, identifies potential drug targets for lung cancer by measuring how compounds alter protein solubility in cells, finding novel targets for 77% of tested molecules.

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Key points

  • ThermoTargetMiner database identifies potential drug targets for lung cancer using the PISA assay.
  • Novel target candidates were found for 77% of 67 tested approved and experimental compounds.
  • The PISA assay differentiates direct drug-target interactions by comparing protein solubility in cell lysates versus living cells.
  • The drug PEITC was verified to exert cytotoxicity by inhibiting its identified pro-target, PAFAH1B.

AI-generated from the title and abstract; the full text is not read.

Abstract

Knowledge of the targets of therapeutic compounds is vital for understanding their action mechanisms and side effects, but such valuable data is seldom available. The multiple complementary techniques needed for comprehensive target characterization must combine data reliability with sufficient analysis throughput. Here, we leveraged the Proteome Integral Solubility Alteration (PISA) assay to characterize the targets of 67 approved and experimental compounds against two main lung cancer subtypes, which is now provided through the website https://thermotargetminer.serve.scilifelab.se/app/thermotargetminer . Novel target candidates (pro-targets) were found for 77% of the tested molecules. Comparison of the protein solubility shifts in lysate vs. living cells highlighted the targets directly interacting with the compounds. We verified that the drug PEITC exerts cytotoxicity through the inhibition of a pro-target PAFAH1B. As PISA is now joining the arsenal of fast and reliable target characterization techniques, the presented database, ThermoTargetMiner, will become a useful resource in lung cancer research.

The authors' abstract, as published at the source. Communications Chemistry, 2026 · DOI ↗

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Field: Spectroscopy

SpectroscopyChemistry